Pharmacovigilance Scope

What is Pharmacovigilance?

Pharmacovigilance is defined as, “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem”.

In some countries, adverse drug reactions (ADRs) rank among the top ten leading causes of mortality. In order to prevent or reduce harm to patients and thus improve public health, mechanisms for evaluating and monitoring the safety of medicines in clinical use are vital. In practice, this means having in place a well-organised pharmacovigilance system, up to phase III of clinical development of INDs, a maximum of 5000 patients are exposed to the new drug. After marketing approval, the number of patients is unlimited. Hence, rare adverse reactions may be newly observed during post-marketing surveillance of the drug.

The principal aims of the pharmacovigilance programme are as follows:

• To improve patient care and safety in relation to the use of medicines, and all medical and para-medical interventions.
• To improve public health and safety in relation to the use of medicines.
• To contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost-effective) use.
• To promote understanding, education and clinical training in pharmacovigilance and its effective communication to health professionals and the public.

Several stakeholders are involved in monitoring the safety of medicines. Some of them are listed below:

• Government
• Pharmaceutical industries
• Hospitals and academia
• Medical and pharmaceutical associations
• Poisons and medicines information centres
• Health professionals like doctors, pharmacists, nurses
• Patients
• Consumers
• The media
• World Health Organisation (WHO)

WHO’s International Drug Monitoring started in 1968. By 2016, 123 countries have joined the programme. WHO headquarters in Geneva is responsible for monitoring the programme. The centre is now known as Uppsala Monitoring Centre (UMC) with the support of the Swedish Government.

Pharmacovigilance in India

The Central Drug Standard Control Organisation (CDSCO), New Delhi, under the control of the Ministry of Health and Family Welfare, the Government of India initiated a nationwide pharmacovigilance programme in July 2010. All Institute of Medical Sciences (AIIMS), New Delhi was the National Co-ordinating Centre (NCC) for monitoring ADRs. Since April 2011, the Indian Pharmacopoeia Commission (IPC), Ghaziabad looks after administrative matters related to NCC. 22 ADR monitoring centres (AMCs) have been established throughout India.

Pharmacovigilance Scope

The scope and objectives of the programme are indicated below:

• To create a nationwide system for patient safety reporting.
• To identify and analyse new signals from the reported cases.
• To analyse the benefit-risk ratio of marketed medications.
• To generate evidence-based information on the safety of medicines.
• To support regulatory agencies in the decision-making process on the use of medications.
• To communicate the safety information on the use of medicines to various stakeholders to minimise the risk.
• To emerge as a national centre of excellence for pharmacovigilance activities.
• To collaborate with other national centres for the exchange of information and data management.
• To provide training and consultancy support to other national pharmacovigilance centres across the globe.
• To identify and analyse new ADR signals from the reported cases.
• To promote rational use of medicines.

There are various regulatory controls over the pharmacovigilance system. The European Medical Agency (EMA) has published elaborate details of Good Pharmacovigilance Practices (GPvP). In addition, USFDA has also published several guidance statements related to pharmacovigilance. The International Council for Harmonisation (ICH) and the Council for International Organisations of Medical Sciences (CIOMS) have published several guidelines related to pharmacovigilance.

There are several pharmacovigilance methods followed in recording adverse events related to drugs. The methods are as follows:

(i) Passive surveillance

Passive surveillance involves collecting reports generated out of the existing system.

• Spontaneous reports: A spontaneous report is an unsolicited communication by healthcare professionals or consumers to a company, regulatory authority or other organisation which describes one or more adverse drug reactions in a patient who was given one or more medicinal products and that does not derive from a study or any organised collection scheme.
• Case series: Series of case reports related to one or more adverse events can provide evidence of an association between a drug and an adverse event. They may be spontaneously reported.

(ii) Stimulated reporting

Several methods like online reporting of adverse events encourage and facilitate reporting by health professionals in specific situations like hospital settings. They are termed as stimulated reporting.

(iii) Active surveillance

Active surveillance seeks to ascertain completely the number of adverse events via a continuous pre-organised process.

• Sentinel sites: By reviewing medical records or interviewing patients and/or physicians in a sample of the selected site, termed sentinel sites, complete and accurate data on reported adverse events can be ensured.
• Drug event monitoring: In drug event monitoring, patients may be identified from electronic prescription data or automated health insurance claims.
• Registries: A registry is a list of patients presenting with the same characteristics; e.g. there can be a registry of diabetic patients.

(iv) Comparative observational studies

There are a number of observation study designs which are useful in validating signals from spontaneous reports or case series.

• Cross-sectional study (Survey): Data collected on a population of patients at a single point in time (or interval of time) regardless of exposure or disease status constitutes a cross-sectional study.
• Case-control study: In the case-control study, cases of disease (or events) are identified. Controls, or patients without the disease or event of interest, are then selected from the source population.
• Cohort study: In a cohort study, a population at risk for the disease (or event) is followed over time for the occurrence of the disease (or event). Information on exposure status is known throughout the follow-up period for each patient.

(v) Targeted clinical investigations

When significant risks are identified from pre-approval clinical trials, further clinical studies might be called for to evaluate the mechanism of action for the adverse reaction. Sometimes, potential risks or un-forcing benefits in special populations (paediatric, geriatric) might be identified from pre-approval clinical trials. To elucidate the benefit-risk profile of a drug outside of a traditional clinical trial setting, a special clinical trial may be conducted. All these trials are termed as targeted clinical investigations.

(vi) Descriptive studies

Descriptive studies are primarily used to obtain the background rate of outcome events and/or establish the prevalence of the use of drugs in specified populations.

• Natural history of disease: The science of epidemiology initially focussed on the natural history of the disease, including characteristics of the disease, patients and distribution of disease in selected populations, as well as estimating the incidence and prevalence of potential outcome of interest. Studies which examine specific aspects of adverse events, like the background incidence rate of or risk factors for the adverse event of interest, can be used to assist in putting spontaneous reports into perspective.
• Drug utilisation study (DUS): DUS describe how a drug is marketed, prescribed, and used in a population, and how these factors influence outcomes, including clinical, social, and economic outcomes. These studies provide data on specific populations, like the elderly, children, or patients with hepatic or renal dysfunction, often stratified by age, gender, concomitant medication, and other characteristics.

All information about the safety of medications has to be communicated to all stakeholders in different ways. Available methods for communication messages are listed in table 1.1.

Table 1.1: Communicating messages about medicine safety

Sr. No	Vehicle	Issued by
1.	“Dear doctor” letters	Pharmaceutical manufacturers.
2.	Medicine alerts	National health authorities.
3.	Media statements	National health authorities/ pharmacovigilance centres.
4.	Patient information leaflets	Pharmaceutical manufacturers/National health authorities/Pharmacovigilance centres.
5.	Newsletters	National pharmacovigilance centres and WHO.
6.	Personal feedback to reporters	National pharmacovigilance centres.

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